Study On The Effects Of Pharmaceutical Excipient Polyethylene Glycol 400 On The Tissue Distribution And Bile Excretion Of Baicalin

Objective: To study the effects of pharmaceutical excipient polyethylene glycol 400(PEG400)on the tissue distribution and bile excretion of baicalin.Methods:(1)The SD rats were randomly divided into baicalin+water and baicalin+PEG400 groups.After the rats were given the corresponding mixed solution,the hearts,liver,spleen and lungs,kidney,stomach,brain,small intestine and bile of the rats were collected at different time points and time periods.The samples were treated with ethyl acetate liquid-liquid and the concentrations of baicalin and its main metabolites in each tissue and bile sample were determined by UPLC-MS/MS.(2)In vitro incubation experiments and enzyme-linked immunosorbent assay(ELISA)were used to study the effects of PEG400 on the enzymatic activities of two-phase metabolic enzymes UGT1A8 and UGT1A9 and their expression in rat liver and small intestine to reveal the mechanism of effects PEG400 on the tissue distribution and bile excretion of baicalin.Results: The established method was validated according to the guidelines issued by the FDA.After investigation,the specificity,precision and accuracy,extraction recovery and matrix effect,and stability of the method under different storage conditions were in line with the requirements of biological sample analysis.(1)In the study of tissue distribution,baicalin and its main metabolite baicalin 6-O-?-D-glucuronide(B6G)were mainly detected in the tissues of rats after gavage of baicalin.The concentration of B6 G in the tissues was higher than that of original drug baicalin,and a small amount of baicalin was detected.The three components were widely distributed in various tissues,and were mainly distributed in tissues with relatively high blood perfusion rates such as stomach,small intestine,kidney and liver.PEG400 increased the concentration of baicalin and B6 G in various tissues to different degrees,and increased the concentration of B6 G more thanbaicalin,but significantly reduced the concentration of baicalin in various tissues.(2)In the bile excretion study,after administration of baicalin in rats,baicalin and its main metabolite B6 G were mainly detected in bile,after PEG400 treatment,which significantly increased the concentration of baicalin and the main metabolite B6 G in bile,but the concentration of the original drug baicalin increased more than B6 G.(3)PEG400 significantly increased the in vitro enzymatic activities of UGT1A8 and UGT1A9 and their concentrations in the liver and small intestine of rats.Conclusion:PEG400 significantly increased the distribution of baicalin in rat tissues and bile excretion,one of the reasons may be related to PEG400 increasing the enzyme activities and expressions of UGT1A8 and UGT1A9,which provided a scientific basis for the reasonable application of pharmaceutical excipient PEG400 and the design of new flavonoid formulations.